Mild‐hyperthermia photothermal therapy (mPTT) has therapeutic potential with minimized damage to normal tissues. However, the poorly vascularized tumor area severely hampers the penetration of photothermal agents (PTAs), resulting in their heterogeneous distribution and the subsequent heterogeneous local temperature during mPTT. The presence of regions below the therapeutic 42 °C threshold can lead to incomplete tumor ablation and potential recurrence. Additionally, tumor anti‐apoptosis and cytoprotection pathways, particularly activated thermoresistance, can nullify mild hyperthermia‐induced tumor damage. Therefore, a bioinspired photosensitizer decorated with leucine to form biomimetic nanoclusters (CP‐PLeu nanoparticles (NPs)) aimed at achieving rapid and homogeneous accumulation in tumors, is introduced. Moreover, CP‐PLeu exhibits photodynamic effects that reverse tumor thermoresistance and physiological repair mechanisms, thereby inhibiting tumor resistance to hyperthermia. With the addition of NIR‐II laser irradiation, CP‐PLeu optimizes the therapeutic efficacy of mPTT and contributes to a minimally invasive therapeutic process for breast cancer. This therapeutic strategy, utilizing a biomimetic photosensitizer for homogeneous distribution of therapeutic temperature and photoactivated reversal of tumor thermoresistance, successfully achieves efficient breast tumor inhibition through an atraumatic mPTT process.

中文翻译：

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仿生光敏剂实现肿瘤热阻逆转，优化乳腺癌无创温和高温光热疗法


温和高温光热疗法（mPTT）具有治疗潜力，可将对正常组织的损伤降至最低。然而，血管化不良的肿瘤区域严重阻碍了光热剂（PTA）的渗透，导致其分布不均匀以及随后在 mPTT 过程中局部温度不均匀。低于 42°C 治疗阈值的区域的存在可能导致肿瘤消融不完全和潜在的复发。此外，肿瘤抗凋亡和细胞保护途径，特别是激活的耐热性，可以消除轻度高热引起的肿瘤损伤。因此，引入了一种用亮氨酸装饰的仿生光敏剂，形成仿生纳米簇（CP-PLeu纳米颗粒（NP）），旨在实现在肿瘤中快速均匀的积累。此外，CP-PLeu表现出光动力效应，可以逆转肿瘤的耐热性和生理修复机制，从而抑制肿瘤对高热的抵抗力。通过添加 NIR-II 激光照射，CP-PLeu 优化了 mPTT 的治疗效果，有助于乳腺癌的微创治疗过程。这种治疗策略利用仿生光敏剂实现治疗温度的均匀分布和光激活逆转肿瘤热阻，通过无创 mPTT 过程成功实现了有效的乳腺肿瘤抑制。